MiR-34 Promotes Autophagy and Apoptosis of Spinal Chondrocytes by Mammalian Target of Rapamycin/Phosphatidylinositol-3-Kinase/Protein Kinase B Signaling

Abstract

Autophagy and apoptosis of chondrocytes participate in spondyloarthritis (SpA). miR-34 involves in various diseases. However, miR-34’s role in autophagy and apoptosis of spine chondrocytes remains unclear. SpA patients and normal bone and articular cartilage tissues were collected, and miR-34 level was detected by Real-time PCR. The chondrocytes of SpA patients were isolated and divided into control group, miR-34 siRNA group and miR-34 group followed by analysis of Caspase 3 activity, cell proliferation by MTT assay, expression of Bax, Bcl-2, ATG5 and Beclin1 by Real time PCR, mTOR/PI3K/AKT signaling pathway protein expression by western blot, as well as TNF-α and IL-6 secretion by ELISA. miR-34 was significantly upregulated in SpA patients compared to normal (P <0.05). miR-34 siRNA transfection into SpA chondrocytes significantly down-regulated miR-34 expression, promoted cell proliferation, decreased Caspase 3 activity and Bax expression, increased Bcl-2, ATG5 and Beclin1 expression, decreased TNF-α and IL- 6 secretion as well as increased pmTOR and pAKT expression (P <0.05). miR-34 mimics was transfected into SpA chondrocytes, which up-regulated miR-34 expression and significantly reversed the above changes (P <0.05). miR-34 is upregulated in SpA patients. Down-regulation of miR-34 inhibits articular chondrocyte apoptosis and promotes autophagy by down-regulatingmTOR/PI3K/AKT signaling pathway, thereby promoting articular chondrocyte proliferation and inhibiting joint inflammation.